Bone age, mineral density, and fatigue damage

Abstract

The most plausible purpose for bone remodeling is to prevent excessive aging of bone, which can cause osteocyte death and increase susceptibility to fatigue microdamage. The age of any particular volume of bone depends on two factors: the probability of remodeling beginning on the nearest bone surface, which is given by the local activation frequency; and the probability of a particular remodeling event penetrating to a specified distance from the surface. These two probabilities can be combined in a mathematical model. According to the model, within about 40 μm from the surface, the rate of surface remodeling is the main determinant of bone age, but beyond 40 μm, the distance from the surface becomes progressively more important. Beyond 75 μm, the bone is essentially isolated from surface remodeling. Application of the model to subjects with and without vertebral fracture indicated that the proportion of iliac cancellous bone with a mean age greater than 20 years was less than 20% in all the control subjects without fracture, but was more than 20% in about one-third of the patients with fracture. Bone age is a major determinant of the degree of mineralization, so that osteoporotic patients with prolonged bone age should have bone of higher true mineral density. Accordingly, mineral density distribution was determined by scanning electron microscopy with backscattered electron imaging, calibrated in terms of atomic number. In osteoporotic patients, the mean atomic number was lower, the proportion of bone with high values was lower, and the proportion of bone with low values was higher than in control subjects, the opposite of what would be predicted by the bone age model just described. These data, together with our failure, to date, to detect osteocyte death and fatigue microdamage in iliac cancellous bone in patients with osteoporosis, cast doubt on the role of low bone turnover and increased bone age in the pathogenesis of vertebral fracture. Although conclusive data are still lacking, bone age, osteocyte death, and fatigue failure are more likely relevant to the pathogenesis of hip fracture. Nevertheless, enhanced bone conservation as a result of modest therapeutic inhibition of remodeling activation more than offsets the hypothetical risk of increasing bone age.